Noninvasive temperature monitoring has many direct uses in diagnosis and therapy. These include aiding in the use of hyperthermia (HT) for treatment of cancer, detection and localization of tumors, diagnosing metabolic abnormalities, and studying muscle exercise and recovery. Noninvasive monitoring of temperature is particularly useful for HT treatment of malignant tumors, where the amount of heat applied depends on the actual temperature in the region and its surroundings. Using the funding from a R21 grant (R21 CA94040) we have developed a noninvasive MR thermometer based on the temperature dependence of hyperfine shifted 1H signal of the paramagnetic lanthanide complex, TmDOTMA-. 1H chemical shifts of TmDOTMA- are approximately 60 times more sensitive to temperature than the water signal and are insensitive to changes in tissue microenvironment such as pH and concentration of other ions and presence of macromolecules. Our preliminary data show that the developed thermometer, based on the proton chemical shift of TmDOTMA-, provides sensitive and accurate methods for monitoring temperature. The overall goal of this R33 proposal is to combine the developed MR thermometry method with other multinuclear MR measurements to investigate the metabolic and physiologic effects HT in experimental tumors during the treatment. The central hypothesis of the proposal is that biological response of tumors, as measured by noninvasive MR spectroscopy and imaging (MRS/MRI) at the time of HT treatment, provides more accurate and reliable information about therapy outcome than HT temperature alone because different tumors or tumor regions have different vulnerability to temperature. To test this hypothesis, robust MR methods will be developed to deliver controlled radiofrequency (RF) HT in the magnet and simultaneously monitor/image the metabolic and physiological effects of HT by in vivo 31P, 23Na, and 1H MRS/MRI. The proposed MR techniques will provide innovative methods to monitor temperature and metabolic/physiologic response to HT treatment during and after the therapy. Application of the proposed techniques to experimental tumors will enhance our understanding of HT biology, which may prove valuable in designing methods to sensitize tumors to HT and other therapies. The animal experiments will be a step toward the application of the proposed techniques to human patients for MRI-guided HT treatment. [unreadable] [unreadable] [unreadable]